In general, humans cannot synthesize β-glucans. Therefore, the immune system recognizes these compounds as foreign. The innate immune system responds to invading
pathogens through pattern recognition receptors (PRR), which are typically expressed by immune cells but also by other cells. PRRs recognize conserved microbial
structures, the so-called microbe-associated molecular patterns (MAMPs), formally called PAMPs. β-glucans are considered as one of the major MAMPs for the
PRR-mediated sensing of fungal infection. So far, the most important PRRs for β-glucans are the dectin-1 receptor, the complement receptor 3 (CR3) and
toll-like-receptors (TLR), which are found on various immune cells such as monocytes, macrophages, dendritic cells, neutrophils, eosinophils, and natural
killer cells, but also on intestinal epithelial cells. Binding of β-glucans to dectin-1 induced a cascade of innate and adaptive immune response such as phagocytosis,
oxidative burst, and the production of cytokines and chemokines in dentritic cells and macrophages. Kankkunen et al. showed that particulate yeast β-glucan triggered
interleukin-1β (IL-1β) mediated cellular response in human primary macrophages via dectin-1 signaling. Earlier in vitro studies showed that yeast β-glucan is a strong
stimulant of macrophages and induced mitogenic activity in rat thymocytes, indicating immunostimulatory effects.

Figure shows: The uptake and subsequent actions of β-glucan on immune cells. Click the image to magnify.

Many investigations on the immunomodulatory effects of β-glucans were performed using parenteral applications. In the meantime, those effects have also been shown
for orally applied β-glucans. Therefore immune stimulating effects may be achieved by dietary intake of yeast β-glucans.

However, not all β-glucan preparations have the potential to stimulate these reactions. In order to be able to activate the dectin-1 receptor cascade, β-glucans
must comply with specific structural properties. It seems that insoluble, particulate (1,3)-β-glucans with 1,6-β-branches are able to activate this cascade, while
soluble ones activate the antibody-mediated complement system via the CR3 receptor.

Clinical trials performed with dietary insoluble particulate β-glucans have demonstrated positive effects on the immune system. Therapeutic efficacy results for
orally applied soluble yeast β-glucans are not yet available. So far, this has only been shown for the insoluble fraction. All the performed
human clinical trials demonstrated that intake of β-glucans is very well tolerated. Based on the clinical trials presented in this review,
an increased intake of dietary β-glucans might help to improve immune functions.